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Pathogenic variants in the\n                    <jats:italic>OGT<\/jats:italic>\n                    gene cause an X\u2010linked congenital disorder of glycosylation (OGT\u2010CDG) presenting developmental delay, hypotonia, intellectual disability, and dysmorphic features. Here, we report on a child with developmental delay, hypotonia, and dysmorphic features who was found to carry a hemizygous novel\n                    <jats:italic>OGT<\/jats:italic>\n                    variant. This child also developed hepatoblastoma by the age of 17\u2009months. OGT\u2010CDG was diagnosed by exome sequencing that identified a de novo missense variant in the\n                    <jats:italic>OGT<\/jats:italic>\n                    gene. Functional validation by Western blot on patient\u2010derived fibroblasts showed reduced O\u2010GlcNAcylation and OGA expression, while significantly reduced enzyme activity in\u00a0vitro confirmed the pathogenicity of the variant. To date, no patients with OGT\u2010CDGs have been reported with hepatoblastoma or other malignancies. Although the occurrence of hepatoblastoma in the proband might be coincidental, the role of O\u2010GlcNAcylation in cancer suggests that the deficiency of OGT activity might be associated with increased cancer risk.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.64275","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T07:10:57Z","timestamp":1759302657000},"page":"502-510","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["An\n                    <scp>\n                      <i>OGT<\/i>\n                    <\/scp>\n                    Missense Variant With Impaired Enzyme Activity in a Child With Severe Developmental Delay and Hepatoblastoma"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1557-415X","authenticated-orcid":false,"given":"Alfonso Manuel","family":"D'Alessio","sequence":"first","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM)  Pozzuoli Italy"},{"name":"Scuola Superiore Meridionale, Genomics and Experimental Medicine Program Federico II University  Naples Italy"},{"name":"Department of Translational Medicine University of Naples \u201cFederico II\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3149-7050","authenticated-orcid":false,"given":"Huijie","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics Aarhus University  Aarhus Denmark"},{"name":"Division of Molecular, Cell and Developmental Biology, School of Life Sciences University of Dundee  Dundee UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandro Raul","family":"Soria","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM)  Pozzuoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4610-3470","authenticated-orcid":false,"given":"Sara Basse","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iolanda","family":"Boffa","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM)  Pozzuoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Arena","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM)  Pozzuoli Italy"},{"name":"Scuola Superiore Meridionale, Genomics and Experimental Medicine Program Federico II University  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedetta","family":"Attianese","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen.","family":"O'Sullivan","sequence":"additional","affiliation":[{"name":"Histology Laboratory, Children's Health Ireland  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noelle","family":"Cullinan","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology &amp; Oncology, Children's Health Ireland  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewis","family":"Pang","sequence":"additional","affiliation":[{"name":"Exeter Genomics Laboratory, RILD Building Royal Devon and Exeter NHS Foundation Trust  Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daan Marinus Ferdinand","family":"van Aalten","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics Aarhus University  Aarhus Denmark"},{"name":"Division of Molecular, Cell and Developmental Biology, School of Life Sciences University of Dundee  Dundee UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6895-8819","authenticated-orcid":false,"given":"Nicola","family":"Brunetti\u2010Pierri","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM)  Pozzuoli Italy"},{"name":"Scuola Superiore Meridionale, Genomics and Experimental Medicine Program Federico II University  Naples Italy"},{"name":"Department of Translational Medicine University of Naples \u201cFederico II\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally Ann","family":"Lynch","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Children's Health Ireland  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.050671"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2009.07.018"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2018.10.45"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adg7492"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.734533"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.102289"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb1079"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1718910115"},{"key":"e_1_2_10_10_1","unstructured":"Ellard S. 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